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1.
BMC Ophthalmol ; 24(1): 208, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715011

RESUMO

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.


Assuntos
Corioide , Angiofluoresceinografia , Miopia , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/patologia , Masculino , Feminino , Adulto Jovem , Miopia/fisiopatologia , Adulto , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Angiofluoresceinografia/métodos , Retina/diagnóstico por imagem , Retina/patologia , Progressão da Doença , Adolescente , Fundo de Olho
2.
Invest Ophthalmol Vis Sci ; 65(5): 17, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717424

RESUMO

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.


Assuntos
Corioide , Degeneração Macular , Drusas Retinianas , Epitélio Pigmentado da Retina , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Corioide/patologia , Corioide/diagnóstico por imagem , Estudos Transversais , Degeneração Macular/diagnóstico , Drusas Retinianas/diagnóstico , Segmento Externo das Células Fotorreceptoras da Retina/patologia , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
3.
Vestn Oftalmol ; 140(2): 5-13, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38742493

RESUMO

Circumscribed choroidal hemangioma (CCH) and early non-pigmented choroidal melanoma (CM) have similar clinical, ultrasound and morphometric features, which in some cases makes their differential diagnosis difficult. There are few studies in the literature devoted to a comparative analysis of the molecular genetic features of CCH and non-pigmented CM, and the results of those studies are contradictory. PURPOSE: This study attempts to develop a method of non-invasive molecular genetic differential diagnostics of CCH and non-pigmented CM. MATERIAL AND METHODS: Based on the results of clinical and instrumental examination methods, 60 patients (60 eyes) with CCH (n=30) and non-pigmented CM (n=30) were included in this prospective study. The control group consisted of 30 individuals without intraocular tumors. Mutations in the GNAQ/GNA11 genes were determined by real-time PCR using the analysis of genomic circulating tumor DNA isolated from peripheral blood plasma. The average follow-up period was 12.1±1.8 months. RESULTS: The study revealed a significant association of mutations in exons 4 and 5 of the GNAQ/GNA11 genes with the presence of non-pigmented CM (27/30; 90%). These mutations were not detected in the group of patients with CCH. Mutations in exons 4 and 5 of the GNAQ/GNA11 genes were also not detected in the control group of healthy individuals. CONCLUSION: This study proposes a method of non-invasive and low-cost differential diagnostics based on molecular genetic analysis and detection of mutations in exons 4 and 5 of the GNAQ and GNA11 genes, which are specific for CM (90%).


Assuntos
Neoplasias da Coroide , Hemangioma , Melanoma , Humanos , Neoplasias da Coroide/genética , Neoplasias da Coroide/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Diagnóstico Diferencial , Hemangioma/genética , Hemangioma/diagnóstico , Adulto , Melanoma/genética , Melanoma/diagnóstico , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Mutação , Corioide/diagnóstico por imagem , Corioide/patologia , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Estudos Prospectivos
4.
Comput Biol Med ; 175: 108386, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691915

RESUMO

Optical Coherence Tomography (OCT) is a commonly used retina imaging technique, and it is capable of revealing the morphology of the choroid. However, the segmentation and quantitative analysis of the sublayers and vessels in choroid are rarely explored, primarily due to the indistinct boundaries of choroidal sublayers, and imbalanced distribution of vessels observed in OCT imagery. In this paper, we propose a novel two-stage architecture called Choroidal Layer Analysis network (CLA), that may be considered the first attempt in this research community for joint segmentation of choroidal sublayers and choroidal vessels in OCT images. CLA employs the encoder-decoder network with the residual U-shape module as the backbone. In order to empower the ability of the segmentation model to identify the inconspicuous boundaries of choroidal sublayers, we introduce an Ambiguous Boundary Attention block (ABA) into the bottleneck of the encoder-decoder network in the first stage. For more accurate segmentation of large choroidal vessels with ambiguous contours and imbalanced spatial distribution, the second stage introduces an active contour-based loss to refine the contours of choroidal vessels simultaneously with precise identification of each vessel via contextual modeling. To train, test and validate the proposed model, we conducted a choroidal segmentation dataset containing 800 OCT images, with their sublayers and large choroidal vessels manually annotated. Experimental results demonstrate the superiority of the proposed approach compared with other state-of-the-art segmentation networks in large margins. It is worth noting that we also reconstructed the large choroidal vessels in three-dimensional (3D) based on the segmentation results, and multiple 3D morphological parameters were calculated. The statistical analysis of these parameters demonstrates significant differences between the healthy control and high myopia group, and this further confirms the proposed work may facilitate subsequent disease understanding and clinical decision-making.


Assuntos
Corioide , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Corioide/diagnóstico por imagem , Corioide/irrigação sanguínea , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
5.
Transl Vis Sci Technol ; 13(5): 16, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767903

RESUMO

Purpose: The purpose of this study was to evaluate the diurnal variation in choroidal parameters in a wide field area among healthy subjects and to identify correlations between choroidal luminal area and stromal area and various systemic factors. Methods: In this cross-sectional study, 42 eyes from 21 healthy participants (mean age = 32.4 ± 8.8 years) were examined using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA, 24 mm × 20 mm). Measurements of choroidal parameters, including choroidal volume (CV), choroidal thickness (CT), choroidal vessel volume (CVV), and choroidal stromal volume (CSV), were taken at 8:00, 12:00, 18:00, and 22:00. Systemic factors, such as blood pressure and heart rate, were concurrently monitored. Results: Our study observed significant diurnal variations in the mean total CV, CT, CVV, and CSV, with minimum measurements around 12:00 (P < 0.001) and peak values at 22:00 (P < 0.001). Furthermore, changes in CV in specific regions were more closely associated with fluctuations in CVV than CSV in the same regions. No significant diurnal variations were found in systolic (P = 0.137) or diastolic blood pressure (P = 0.236), whereas significant variations were observed in the heart rate (P = 0.001). Conclusions: Our study reveals diurnal variations in choroidal parameters and their associations, emphasizing that changes in choroidal volume relate more to the luminal than the stromal area in vessel-rich regions. This enhances our understanding of choroidal-related ocular diseases. Translational Relevance: Regions with higher choroidal vasculature observed greater choroidal volume changes.


Assuntos
Corioide , Ritmo Circadiano , Voluntários Saudáveis , Tomografia de Coerência Óptica , Humanos , Corioide/diagnóstico por imagem , Corioide/irrigação sanguínea , Corioide/anatomia & histologia , Tomografia de Coerência Óptica/métodos , Masculino , Adulto , Feminino , Estudos Transversais , Ritmo Circadiano/fisiologia , Adulto Jovem , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Angiofluoresceinografia/métodos , Pessoa de Meia-Idade
6.
Clin Exp Med ; 24(1): 98, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727918

RESUMO

The role of mast cells in physiologic and pathological processes extends far beyond the allergy processes: they are involved in wound healing, chronic inflammation, and tumor growth. This short article emphasizes the role played by mast cells in age-related macular degeneration (AMD). Mast cells can induce angiogenesis and are present around Bruch's membrane during the early and late stages of choroidal neovascularization in AMD. Proteolytic enzymes released by mast cells lead to thinning of the choroid in AMD as well as degradation of vascular basement membranes and Bruch's membrane, which in turn could result in retinal pigment epithelial death and choriocapillaris degeneration in geographical atrophy and exudative AMD.


Assuntos
Corioide , Degeneração Macular , Mastócitos , Humanos , Corioide/patologia , Degeneração Macular/patologia , Degeneração Macular/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/metabolismo , Lâmina Basilar da Corioide/patologia , Lâmina Basilar da Corioide/metabolismo
7.
Sci Rep ; 14(1): 11382, 2024 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762668

RESUMO

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.


Assuntos
Calcitriol , Miopia , Retina , Animais , Cobaias , Miopia/metabolismo , Miopia/tratamento farmacológico , Miopia/patologia , Calcitriol/farmacologia , Retina/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/genética , Masculino , Modelos Animais de Doenças , Esclera/metabolismo , Esclera/efeitos dos fármacos , Esclera/patologia , Corioide/metabolismo , Corioide/efeitos dos fármacos , Corioide/patologia , Vitamina D/farmacologia , Vitamina D/administração & dosagem , Comprimento Axial do Olho , Corpo Vítreo/metabolismo , Corpo Vítreo/efeitos dos fármacos , Progressão da Doença , Colágeno/metabolismo
8.
Biochem Biophys Res Commun ; 718: 150078, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38735140

RESUMO

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.


Assuntos
Cloretos , Corioide , Transporte de Íons , Epitélio Pigmentado da Retina , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/efeitos da radiação , Epitélio Pigmentado da Retina/patologia , Corioide/metabolismo , Corioide/efeitos da radiação , Corioide/patologia , Animais , Transporte de Íons/efeitos da radiação , Cloretos/metabolismo , Iluminação/métodos , Temperatura , Cor , Junções Íntimas/metabolismo , Miopia/metabolismo , Miopia/patologia , Miopia/etiologia
9.
BMC Ophthalmol ; 24(1): 212, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750496

RESUMO

BACKGROUND: To evaluate differences in log MAR best-corrected visual acuity (BCVA) improvement and postoperative central foveal thickness (CFT) and choroidal thickness (CT) changes between conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS) for high-myopia cataracts. METHODS: This was a retrospective and observational study. One hundred and two eyes of 102 patients with high-myopia cataracts were examined. CPS was performed in 54 eyes, and FLACS was performed in 48 eyes. All eyes underwent logMAR BCVA, CFT and CT of three different sectors preoperatively and one week and six months postoperatively. RESULTS: The logMAR BCVA improved significantly after surgery in both groups (both P < 0.001), but no difference was observed in BCVA improvement between the groups (P = 0.554). Moreover, no significant differences were reflected in the changes in CFT, nasal 1 mm CT or temporal 1 mm CT between the two groups, and only subfoveal choroidal thickness (SFCT) in the CPS group decreased significantly compared with that in the FLACS group at any postoperative time (P = 0.003 and 0.026). AL, preoperative logMAR BCVA, and CT of the three regions exhibited a notable correlation with postoperative BCVA (all P < 0.05) according to univariate logistic regression analysis. However, only the AL, preoperative logMAR BCVA and SFCT remained significant in the multivariate model. Postoperative logMAR BCVA revealed a positive correlation with AL and preoperative logMAR BCVA but a negative correlation with SFCT. CONCLUSIONS: FLACS was not superior to CPS in improving BCVA but had less impact on SFCT in the treatment of high-myopia cataracts. Eyes with a longer AL, worse preoperative logMAR BCVA and thinner SFCT had a high risk of worse postoperative BCVA.


Assuntos
Catarata , Terapia a Laser , Facoemulsificação , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Estudos Retrospectivos , Feminino , Masculino , Facoemulsificação/métodos , Acuidade Visual/fisiologia , Pessoa de Meia-Idade , Idoso , Terapia a Laser/métodos , Catarata/complicações , Catarata/fisiopatologia , Tomografia de Coerência Óptica/métodos , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Extração de Catarata/métodos , Miopia Degenerativa/fisiopatologia , Miopia Degenerativa/cirurgia , Miopia Degenerativa/complicações , Corioide/diagnóstico por imagem , Resultado do Tratamento
11.
Vestn Oftalmol ; 140(2. Vyp. 2): 16-20, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38739126

RESUMO

Optical coherence tomography (OCT) is currently widely used for the diagnosis of choroidal melanoma (CM), but the problem of predicting the outcomes of planned CM treatment remains unsolved. PURPOSE: This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment. MATERIAL AND METHODS: OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account. RESULTS: Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction. CONCLUSION: When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.


Assuntos
Braquiterapia , Neoplasias da Coroide , Melanoma , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Neoplasias da Coroide/terapia , Neoplasias da Coroide/diagnóstico , Melanoma/terapia , Melanoma/diagnóstico , Melanoma/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Braquiterapia/métodos , Prognóstico , Hipertermia Induzida/métodos , Resultado do Tratamento , Tratamentos com Preservação do Órgão/métodos , Adulto , Corioide/diagnóstico por imagem , Corioide/patologia , Idoso , Valor Preditivo dos Testes
12.
Immunohorizons ; 8(5): 363-370, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38775688

RESUMO

Although the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2RFPCx3cr1GFP dual-reporter mice and immunostaining techniques to confirm localization of NLRP3 inflammasomes in the laser-induced CNV (LCNV) lesions. Confocal microscopy was used to image and quantify LCNV volumes. MCC950 was used as NLRP3 inhibitor. ELISA and quantitative RT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1ß protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (-/-) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that red fluorescent protein (RFP)-positive monocyte-derived macrophages and GFP-positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post-laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2RFP-positive macrophages, Cx3cr1GFP-positive microglia, and other cells, resulting in an increase in total lesion size. NLRP3 (-/-) LCNV mice showed significantly increased lesion size compared with age-matched controls. Inhibition of NLRP3 resulted in decreased IL-1ß mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1ß.


Assuntos
Neovascularização de Coroide , Indenos , Inflamassomos , Interleucina-1beta , Microglia , Monócitos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Camundongos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Microglia/metabolismo , Monócitos/metabolismo , Camundongos Knockout , Sulfonas/farmacologia , Camundongos Endogâmicos C57BL , Furanos/farmacologia , Receptores CCR2/metabolismo , Receptores CCR2/genética , Macrófagos/metabolismo , Macrófagos/imunologia , Sulfonamidas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Corioide/metabolismo , Corioide/patologia , Modelos Animais de Doenças , Lasers/efeitos adversos , Degeneração Macular/patologia , Degeneração Macular/metabolismo , Degeneração Macular/genética
13.
Front Immunol ; 15: 1379586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745648

RESUMO

Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.


Assuntos
Neovascularização de Coroide , NF-kappa B , Transdução de Sinais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/genética , Animais , Camundongos , Humanos , NF-kappa B/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Macrófagos/imunologia , Corioide/metabolismo , Corioide/patologia , Corioide/irrigação sanguínea , Masculino , Degeneração Macular Exsudativa/metabolismo , Degeneração Macular Exsudativa/genética , Degeneração Macular Exsudativa/patologia , Inflamação/metabolismo , Citocinas/metabolismo
14.
Invest Ophthalmol Vis Sci ; 65(4): 8, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568620

RESUMO

Purpose: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Methods: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery. Results: RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Conclusions: Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.


Assuntos
Neovascularização de Coroide , Atrofia Geográfica , Degeneração Macular , Feminino , Suínos , Animais , Desbridamento , Degeneração Macular/diagnóstico , Degeneração Macular/cirurgia , Atrofia Geográfica/diagnóstico , Sus scrofa , Retina , Corioide , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/cirurgia
15.
Acta Neuropathol ; 147(1): 71, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607446

RESUMO

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.


Assuntos
Hamartoma , Neurofibromatose 1 , Humanos , Criança , Neurofibromatose 1/complicações , Corioide/diagnóstico por imagem , Autopsia
16.
Invest Ophthalmol Vis Sci ; 65(4): 14, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578621

RESUMO

Purpose: This study aims to examine the short-term peripheral choroidal thickness (PChT) response to signed defocus blur, both with and without native peripheral aberrations. This examination will provide insights into the role of peripheral aberration in detecting signs of defocus. Methods: The peripheral retina (temporal 15°) of the right eye was exposed to a localized video stimulus in 11 young adults. An adaptive optics system induced 2D myopic or hyperopic defocus onto the stimulus, with or without correcting native peripheral ocular aberrations (adaptive optics [AO] or NoAO defocus conditions). Choroidal scans were captured using Heidelberg Spectralis OCT at baseline, exposure (10, 20, and 30 minutes), and recovery phases (4, 8, and 15 minutes). Neural network-based automated MATLAB segmentation program measured PChT changes from OCT scans, and statistical analysis evaluated the effects of different optical conditions over time. Results: During the exposure phase, NoAO myopic and hyperopic defocus conditions exhibited distinct bidirectional PChT alterations, showing average thickening (10.0 ± 5.3 µm) and thinning (-9.1 ± 5.5 µm), respectively. In contrast, induced AO defocus conditions did not demonstrate a significant change from baseline. PChT recovery to baseline occurred for all conditions. The unexposed fovea did not show any significant ChT change, indicating a localized ChT response to retinal blur. Conclusions: We discovered that the PChT response serves as a marker for detecting peripheral retinal myopic and hyperopic defocus blur, especially in the presence of peripheral aberrations. These findings highlight the significant role of peripheral oriented blur in cueing peripheral defocus sign detection.


Assuntos
Hiperopia , Miopia , Adulto Jovem , Humanos , Miopia/diagnóstico , Hiperopia/diagnóstico , Corioide , Retina , Fóvea Central , Refração Ocular
17.
BMJ Open Ophthalmol ; 9(1)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589233

RESUMO

OBJECTIVE: This study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia. METHODS AND ANALYSIS: In this longitudinal investigation, 431 eyes-342 categorised as non-high myopia (non-HM) and 89 as HM-were examined for 2 years. Participants were examined with swept-source optical coherence tomography. The macular ChT, PPA area and axial length (AL) were measured at baseline and follow-up visits. Multiple regression analysis was performed to identify factors associated with ChT changes. The areas under the receiver operating characteristic curves were analysed to ascertain the predictive capacity of the PPA area and axial elongation for the reduction in macular ChT. RESULTS: Initial measurements revealed that the average macular ChT was 240.35±56.15 µm in the non-HM group and 198.43±50.27 µm in the HM group (p<0.001). It was observed that the HM group experienced a significantly greater reduction in average macular ChT (-7.35±11.70 µm) than the non-HM group (-1.85±16.95 µm, p=0.004). Multivariate regression analysis showed that a greater reduction of ChT was associated with baseline PPA area (ß=-26.646, p<0.001) and the change in AL (ß=-35.230, p<0.001). The combination of the baseline PPA area with the change in AL was found to be effective in predicting the decrease in macular ChT, with an area under the curve of 0.741 (95% CI 0.694 to 0.787). CONCLUSION: Over 2 years, eyes with HM exhibit a more significant decrease in ChT than those without HM. Combining the baseline PPA area with the change in AL could be used to predict the decrease of macular ChT.


Assuntos
Miopia , Humanos , Adulto Jovem , Miopia/diagnóstico por imagem , Corioide/diagnóstico por imagem , Nervo Óptico , Análise Multivariada , Atrofia/complicações
18.
Transl Vis Sci Technol ; 13(4): 17, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38591943

RESUMO

Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.


Assuntos
Aprendizado Profundo , Demência Frontotemporal , Glaucoma , Miopia , Humanos , Estudos Transversais , Estudos Retrospectivos , Glaucoma/complicações , Glaucoma/diagnóstico , Miopia/complicações , Miopia/diagnóstico , Atrofia , Corioide
19.
Sci Rep ; 14(1): 8339, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594294

RESUMO

Choroideremia (CHM) is an X-linked retinal degeneration leading to loss of the photoreceptors, retinal pigment epithelium (RPE), and choroid. Adaptive optics optoretinography is an emerging technique for noninvasive, objective assessment of photoreceptor function. Here, we investigate parafoveal cone function in CHM using adaptive optics optoretinography and compare with cone structure and clinical assessments of vision. Parafoveal cone mosaics of 10 CHM and four normal-sighted participants were imaged with an adaptive optics scanning light ophthalmoscope. While acquiring video sequences, a 2 s 550Δ10 nm, 450 nW/deg2 stimulus was presented. Videos were registered and the intensity of each cone in each frame was extracted, normalized, standardized, and aggregated to generate the population optoretinogram (ORG) over time. A gamma-pdf was fit to the ORG and the peak was extracted as ORG amplitude. CHM ORG amplitudes were compared to normal and were correlated with bound cone density, ellipsoid zone to RPE/Bruch's membrane (EZ-to-RPE/BrM) distance, and foveal sensitivity using Pearson correlation analysis. ORG amplitude was significantly reduced in CHM compared to normal (0.22 ± 0.15 vs. 1.34 ± 0.31). In addition, CHM ORG amplitude was positively correlated with cone density, EZ-to-RPE/BrM distance, and foveal sensitivity. Our results demonstrate promise for using ORG as a biomarker of photoreceptor function.


Assuntos
Coroideremia , Humanos , Oftalmoscopia/métodos , Células Fotorreceptoras Retinianas Cones , Corioide , Epitélio Pigmentado da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos
20.
Invest Ophthalmol Vis Sci ; 65(4): 22, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38597724

RESUMO

Purpose: Studies report conflicting findings regarding choroidal thickness changes in response to myopic defocus in humans. This study aimed to investigate the choroidal response to myopic defocus in children and adults using automated analysis. Methods: Participants (N = 46) were distance-corrected in both eyes and viewed a movie on a screen for 10 minutes. Two optical coherence tomography (OCT) radial scans were collected for each eye, then +3 diopters was added to one eye. Participants continued to watch the movie, OCT scans were repeated every 10 minutes for 50 minutes, and then recovery was assessed at 60 and 70 minutes. Defocus was interrupted for approximately two out of each 10 minutes for OCT imaging. OCT images were analyzed using an automated algorithm and trained neural network implemented in MATLAB to determine choroidal thickness at each time point. Repeated-measures ANOVA was used to assess changes with time in three age groups (6-17, 18-30, and 31-45 years) and by refractive error group (myopic and nonmyopic). Results: Choroidal thickness was significantly associated with spherical equivalent refraction, with the myopic group having a thinner choroid than the nonmyopic group (P < 0.001). With imposed myopic defocus, there were no significant changes in choroidal thickness at any time point for any age group and for either refractive error group (P > 0.05 for all). Conclusions: Findings demonstrate that, using the described protocol, the choroidal thickness of children and adults does not significantly change in response to short-term, full-field myopic defocus, in contrast to several previously published studies.


Assuntos
Miopia , Erros de Refração , Adulto , Criança , Humanos , Miopia/diagnóstico , Corioide , Refração Ocular , Tomografia de Coerência Óptica
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